Studies have linked certain dietary factors with atherosclerosis, a forerunner of coronary heart disease (Addis, P. B., Carr, T. P., Hassel, C. A., Hwang, Z. Z., Warner, G. J., Atherogenic and anti-atherogenic factors in the human diet. Biochem. Soc. Symp. 61, 259-271 (1995)). For example, a diet high in polyunsaturated fatty acids (PUFAS) may render low-density lipoprotein (LDL) more susceptible to peroxidation (Addis et al. 1995). The peroxidation of LDL can cause tissue damage leading to atherosclerosis (Sarkkinen, E. S., Uusitupa, M. I. J., Nyyssonen, K., Parviainen, M., Penttila, I., Salonen, J. T., Effects of two low-fat diets, high and low in polyunsaturated fatty acids, on plasma lipid peroxides and serum vitamin E levels in free-living hypercholesterolaemic men. European Journal of Clinical Nutrition (1993) 47: 623-630). The peroxidation of LDL is a result of the neutrophilic production of a superoxide anion radical or other reactive species (Steinberg, D., Parthasapathy, S., Carew, T. E., Khoo, J. C., Witztum, J. L. (1989) Beyond cholesterol. Modifications of low-density lipoprotein that increases its atherogenicity. New England Journal of Medicine 320: 915-924). The reactive species produced interact with PUFAS to form lipid peroxyl radicals, which subsequently produce lipid hydroperoxides and additional lipid peroxyl radicals (Steinberg et al. 1989). This initiates a peroxidative cascade which may eventually modify an essential part of the lipid's membrane, causing changes in membrane permeability and even cell death (Steinberg et al. 1989). Peroxidative degradation of LDL also leads to the formation of lipid oxidation products such as malondialdehyde (MDA) and other aldehydes which may be potentially toxic to the cell (Steinberg et al. 1989).
Oxidative stress has been implicated in a variety of diseases and pathological conditions, including endothelial cell cytotoxicity, coronary heart diseases (such as thrombosis and hyperlipemia) and cancer. (Addis et al. 1995). Recent studies have shown that elevated lipid peroxidation levels (oxidative stress) may play a role in the pathogenesis of Alzheimer's disease which includes a group of neurodegenerative disorders with diverse etiologies, but the same hallmark brain lesions. Practico D. et al., Increased F2-isoprostanes in Alzheimer's disease: evidence for enhanced lipid peroxidation in vivo. FASEB J. 1998 Dec.; 12 (15): 1777-1783.
Clinical studies have established that elevated plasma concentrations of LDL are associated with atherosclerosis, a most prevalent cardiovascular disease and the principle cause of heart attack, stroke and vascular circulation problems (Sarkkinen et al. 1993). It is believed that a reduction of atherogenic lipid peroxides (which are transported in the LDL fraction of blood serum) can reduce the risk of atherogenesis (Mazur, A., Bayle, D., Lab, C., Rock, E., Rayssiguier, Y., Inhibiting effect of procyanidin-rich extracts on LDL oxidation in vitro. Atherosclerosis 145 (1999) 421-422). Antioxidants limit oxidative modification of LDL and consequently lower plasma concentrations of LDL, thereby acting as anti-atherogenic compounds (Sarkkinen et al. 1993). The oxidation of LDL has been reported as a model for testing the ability of polyphenols to act as antioxidants by breaking the peroxidative cascade described above (Rice-Evans, C., Plant polyphenols: free radical scavengers or chain-breaking antioxidants? Biochem. Soc. Symp. 61, 103-116 (1995)). Studies have reported that polyphenols can break the chain of the peroxidative process by intercepting free radicals before they reenter the cycle (Rice-Evans 1995).